1. Technical Field
This invention relates to methods for non-invasively determining biological tissue oxygenation in general, and to non-invasive methods utilizing near-infrared spectroscopy (NIRS) techniques for determining the same in particular, especially for lower gastrointestinal (GI) oxygenation for a newborn baby.
2. Background Information
U.S. Pat. No. 6,456,862 and U.S. patent application Ser. No. 10/628,068, both assigned to the assignee of the present application and both hereby incorporated by reference, disclose methods for spectrophotometric blood oxygenation monitoring. Oxygen saturation within blood is defined as:
                                          O            2                    ⁢                                          ⁢          saturation          ⁢                                          ⁢          %                =                                                            Hb                ⁢                O                            2                                      (                                                                    Hb                    ⁢                    O                                    2                                +                Hb                            )                                *          100          ⁢          %                                    (                  Eqn          .                                          ⁢          1                )            These methods, and others known within the prior art, utilize variants of the Beer-Lambert law to account for optical attenuation in tissue at a particular wavelength. Relative concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb), and therefore oxygenation levels, within a tissue sample are determinable using changes in optical attenuation:
                              Δ          ⁢                                          ⁢                      A            λ                          =                              -                                          log                ⁡                                  (                                                            I                                              t                        ⁢                                                                                                  ⁢                        2                                                                                    I                                              t                        ⁢                                                                                                  ⁢                        1                                                                              )                                            λ                                =                                    α              λ                        *            Δ            ⁢                                                  ⁢            C            *            d            *                          B              λ                                                          (                  Eqn          .                                          ⁢          2                )            wherein “Aλ” represents the optical attenuation in tissue at a particular wavelength λ (units: optical density or OD); “I” represents the incident light intensity (units: W/cm2); “αλ” represents the wavelength dependent absorption coefficient of the chromophore (units: OD*cm−1*μM−1); “C” represents the concentration of chromophore (units: μM); “d” represents the light source to detector (optode) separation distance (units: cm); and “Bλ” represents the wavelength dependent light scattering differential pathlength factor (unitless). The term “chromophore’ as used herein is a material, substance, or molecule that absorbs certain wavelengths of light and reflects others, which results in visible detection of a color (e.g., HbO2 appears reddish in color and Hb appears bluish in color).
To non-invasively determine oxygen saturation within tissue accurately, it is necessary to account for the optical properties (e.g., absorption coefficients or optical densities) of the tissue being interrogated. In some instances, the optical properties for the tissue components that create background light absorption and scattering can be assumed to be relatively constant over a selected wavelength range. In other instances, they cannot accurately be assumed to be constant. FIG. 1 illustrates an example of the relationship between the optical properties of tissue and the scattering losses and the background tissue absorption losses.
In some instances, the region of the subject being interrogated may contain chromophores other than Hb and HbO2, which unless accounted for, can adversely affect the determination of Hb and HbO2. When NIRS techniques are used to monitor lower GI oxygenation in neonates, for example, chromophores to be accounted for include components of neonatal meconium stools, transitional stools, and certain nutritional fluids, all of which have a wavelength dependent absorption spectra in the same wavelength range as Hb and HbO2, as shown in FIG. 1. A NIRS algorithm that does not compensate for neonatal stools, particularly meconium, will very likely give an inaccurate measurement of lower GI tissue oxygenation. Specifically, the inaccurate measurement will often erroneously indicate a decreased lower GI oxygenation level, because the absorption spectra of meconium and certain nutritional fluids mimics deoxygenated hemoglobin (Hb).
Meconium stools are typically passed by a neonate during its first two or three days of life. Meconium stools are quickly followed by transitional stools by in the 4 to 5 days of age range. Meconium is a composite of desquamated intestinal lining, mucous, blood and bile. Bilirubin and biliverdin found within liver bile can influence the color of a stool when present within the stool. Bilirubin is formed by the liver from hemoglobin that is released during the end of life-cycle for red blood cells. Referring to FIG. 2, as hemoglobin is broken down, heme is converted to biliverdin by heme oxygenase. Then biliverdin is converted to bilirubin by biliverdin reductase. Depending on the concentration of bilirubin and biliverdin, bile can vary from almost black to green and light yellow in color. A fresh specimen of day-old meconium has been determined to typically have a peak transmittance (i.e. low light absorption) of about 900 nm. While the composition of meconium is unique in its high concentration of bile and other aspects, follow-on stools such as transitional stools may also have chromophores in or near the absorbance range associated with Hb and HbO2. In particular high concentrations of biliverdin in transitional stools, which makes the stool appear green in color, has a distinctive absorbance spectra, similar to that of meconium as shown in FIG. 3. The absorbance spectra of isolated biliverdin as shown in FIG. 3A demonstrates this characteristic, while the absorption spectra of isolated bilirubin (see FIG. 3B) does not. Because bile is present in the liver and gall bladder which can contain biliverdin, high concentrations of bile can adversely affect the determination of Hb and HbO2 by NIRS monitoring of these organs as well.
Iron containing fluids commonly used to meet the enterally delivered nutritional needs of infants (e.g., breast milk and infant formula) are examples of nutritional fluids. While the exact chemical makeup of breast milk is still unknown, the composition of infant formula is formulated to be similar to the generally accepted makeup. An example of the mismatch between breast milk and formula that is pertinent to the present application is the amount and uptake of iron; e.g., breast milk contains about 0.3 mg of iron per liter, of which nearly half is absorbed, and formula contains about 10 mg of iron per liter, of which less than 5% is absorbed. Iron salts are the common source for fortifying infant formula (ferrous fumarate, ferrous sulfate, and ferrous gluconate). Other chromophores are likely present in these two fluids. In addition to iron, the U.S. Food and Drug Administration (FDA) specifies that infant formula must contain: fat, protein, niacin, folic acid, linoleic acid, pantothenic acid, calcium, chloride, copper, iodine, manganese, magnesium, phosphorous, potassium, sodium, and zinc, and vitamins A, B, B1, B2, B12, C, D, E, and K. In addition, formulas not made with cow's milk must include biotin, choline and inositol. A formula frequently given to neonates during a neonate intensive care unit stay is Enfamil® brand infant formula (iron fortified, premature lipil) marketed by Mead Johnson & Company. The Enfamil® formula was found to have a peak transmittance of about 850 nm. The term “transmittance”, as used herein, refers to the amount of light that passes through the material; i.e., the inverse of absorbance.
The timing and volume of enteral nutrition by caregivers is rather subjective, especially for infants at risk for bowel-related diseases, e.g., necrotizing enterocolitis (NEC) and perforation of the gastrointestinal tract. While the etiology of these diseases is mixed and not fully understood, it is believed that ischemia plays a common critical role. Until enteral feeds are tolerated, parenteral or intravenous sources of nutrition are administered (a more invasive and largely less effective methodology).
What is needed, therefore, is a method for non-invasively determining the level of oxygen saturation and related ischemia within lower GI tissue, which method is operable to account for materials potentially within the lower GI tract that have a wavelength dependent absorption spectra (e.g., meconium, including stool components such as biliverdin, and/or nutritional fluids, etc.) that would, if unaccounted for, affect the accuracy of the oxygen saturation determination.
What is also needed, therefore, is a method for non-invasively determining the level of oxygen saturation and related ischemia within the viscera (GI, liver, kidneys, pancreas, stomach), which method is operable to account for materials potentially within the viscera that have a wavelength dependent absorption spectra (certain nutritional fluids) that would, if unaccounted for, affect the accuracy of the oxygen saturation determination.